Wheat germ agglutinin-conjugated PLGA nanoparticles for the delivery of paclitaxel

Abstract

Wheat germ agglutinin (WGA)-conjugated PLGA nanoparticles (NP) were prepared in this project to improve paclitaxel chemotherapy based on the preferential agglutination of WGA to malignant lung cells. Uptake of WGA-conjugated PLGA NP by A549 cells at 37A?C was 7.84-fold higher than control NP at loading concentration of 5.3 mg/ml. Uptake occurred by WGA receptor-mediated endocytosis, with apparent involvement of the caveolae. Paclitaxel loaded into the WGA PLGA NP showed superior in vitro cytotoxicity on A549 and H1299 cells compared with control formulations. Cytotoxicity was further enhanced by incorporating release-enhancing agent isopropyl myristate. Unlike the clinical paclitaxel formulation, IC50 for the paclitaxel-loaded WGA-PLGA NP was not dependent on incubation time (14 and 17 mM at 5 and 24h, respectively). The in vitro results were corroborated by in vivo data obtained from the SCID mice tumor model. Doubling time for the grafted A549 tumor was >25 days for the WGA-PLGA NP formulation relative to 14 days for the clinical formulation. The combined data suggest that the WGA-conjugated PLGA NP could be a promising delivery platform for paclitaxel.